The long term objective of this proposal is to examine carcinogenic perturbation of the transforming ability of viruses. Particular attention is being paid to the environmental carcinogens, the N-nitroso compounds. We are exploiting cocarcinogenic in vivo interactions and we are also measuring the effect of carcinogen on certain in vitro parameters of transformation. These latter experiments can be used to predict the in vivo behavior of transformed cell populations. The current studies have devoted a large effort to the characterization of the enzyme plasminogen activator (PA) as a parameter of oncogenic transformation for cells transformed by herpes simplex virus type II (HSV-2). A strong positive correlation has been established to show that increased PA activity is predictive for the increased ability of a transformed cell population to form a tumor after subcutaneous injection of newborn hamsters. More importantly, for HSV-transformed cells, increased levels of this enzyme indicate that the resulting primary tumor will metastasize to lung tissue more rapidly and more extensively. Experiments are now in progress to use PA expression as a predictive enzyme to determine the effect of N-nitroso compound exposure on HSV-2 transformed cells.